In chemotherapy for cancer, various antitumor agents such as microtubule agonists such as taxanes, Vinca alkaloids and the like; topoisomerase inhibitors; alkylating agents and the like are used. These antitumor agents have various problems, for example, the types of cancer for which these antitumor agents can be used are limited, adverse effects such as myelotoxicity, neuropathy and the like are observed, drug-resistant tumors emerge, and the like (Nature Reviews Cancer 2003, 3, 502). Recently, a molecular targeted antitumor agent showing effectiveness against a specific type of cancer has been reported. Imatinib or gefitinib, which is a tyrosine kinase inhibitor, shows effectiveness also in chronic myeloid leukemia or non-small-cell lung cancer against which existing antitumor agents are ineffective. However, the types of cancer against which the agent shows effectiveness are limited, and also, a case where acquisition of resistance is observed has been reported (Nature Reviews Drug Discovery 2004, 3, 1001). Therefore, a novel antitumor agent in which such problems are improved has been demanded.
Wnt/β-catenin signaling is an important pathway associated with development, differentiation, and maintenance of living organisms (Nature Reviews Drug Discovery 2006, 5, 997). On the other hand, it is known that abnormal Wnt/β-catenin signaling is also associated with various diseases such as cancer and the like. In the absence of Wnt signaling, cytoplasmic β-catenin is kept at a low level. Axin and Adenomatous Polyposis Coli (APC) form a scaffold to accelerate the phosphorylation of intracellular β-catenin by casein kinase 1α (CK1α) and glycogen synthase kinase 3β (GSK3β). The phosphorylated β-catenin is ubiquitinated and degraded by proteasome. Due to this, β-catenin is kept at a low level, and therefore cannot play a role as a transcriptional activator. In the presence of a Wnt ligand, when the Wnt ligand binds to a Frizzled (Fzd) receptor and a low-density lipoprotein receptor-related protein (LRP) receptor, an Axin-APC-CK1α-GSK3β complex is inactivated through Deshevelled (Dv1). Dephosphorylated β-catenin is stable and is accumulated in cells and transferred to the nucleus, and then binds to a T-cell factor (Tcf)/lymphoid enhancer factor (Lef) family transcription factor. This transcription factor complex induces the transcriptional activation of various target genes associated with proliferation, survival, and differentiation of cells.
Abnormal activation of Wnt/β-catenin signaling has been reported in various tumor tissues. The activation of Wnt/β-catenin signaling in a tumor is associated with a gene mutation of a molecule constituting this signaling or an increase or decrease in the expression level of a gene product thereof (Nature Reviews Drug Discovery 2006, 5, 997, Nature Reviews Cancer 2008, 8, 387). For example, in large bowel cancer and familial adenomatous polyposis coli, an APC gene loss-of-function mutation has been reported. In large bowel cancer, hepatocellular carcinoma, hepatoblastoma, and medulloblastoma, an Axin gene loss-of-function mutation has been reported. In large bowel cancer, stomach cancer, hepatocellular carcinoma, hepatoblastoma, Wilms' tumor, ovarian cancer, and pancreatic cancer, a β-catenin gene gain-of-function mutation has been reported. In large bowel cancer, breast cancer, melanoma, head and neck cancer, non-small-cell lung cancer, stomach cancer, mesothelioma, and pancreatic cancer, an increase in the expression of a Wnt ligand has been reported. In large bowel cancer, breast cancer, head and neck cancer, stomach cancer, synovial sarcoma, and pancreatic cancer, an increase in the expression of a Fzd receptor has been reported. In mesothelioma, non-small-cell lung cancer, and cervical cancer, an increase in the expression of a Dvl family member has been reported. In large bowel cancer, breast cancer, stomach cancer, mesothelioma, non-small-cell lung cancer, prostate cancer, esophageal cancer, and leukemia, a decrease in the expression of a secreted frizzled-related protein (SFRP) family member, which is a Wnt ligand inhibitory factor, has been reported. In large bowel cancer, breast cancer, prostate cancer, lung cancer, bladder cancer, and mesothelioma, a decrease in the expression of a Wnt inhibitory factor (WIF) family member has been reported. The inhibition of Wnt/β-catenin signaling inhibits the proliferation of a cancer cell line in which Wnt/β-catenin signaling is activated in this manner (Cell 2002, 111, 241, Oncogene 2005, 24, 3054, Neoplasia 2004, 6, 7, Clinical Cancer Research 2003, 9, 1291, Cancer Research 2004, 64, 5385, Cancer Cell 2004, 5, 91, Proceedings of the National Academy of Sciences of the U.S. Pat. No. 2,004,101, 12682). Therefore, a molecule that inhibits Wnt/β-catenin pathway is considered to be promising as an antitumor agent. There has been a report that diseases other than cancer including pulmonary fibrosis, fibromatosis, and osteoarthritis are associated with Wnt/β-catenin signaling (The American Journal of Pathology 2003, 162, 1393, Proceedings of the National Academy of Sciences of the United States of America 2002, 99, 6973, Proceedings of the National Academy of Sciences of the U.S. Pat. No. 2,004,101, 9757). Therefore, a molecule that inhibits Wnt/β-catenin pathway is expected to be useful as a therapeutic agent in these fields.
As a compound that inhibits Wnt/β-catenin signaling, a tankyrase inhibitor has been reported (Nature 2009, 461, 614). Tankyrase belongs to the family of poly-(ADP-ribose) polymerases (PARP), and is also known as “PARP5” (Nature Reviews Molecular Cell Biology 2006, 7, 517). It has been reported that tankyrase binds to Axin which is associated with the degradation of cytoplasmic β-catenin to perform poly-ADP ribosylation, thereby accelerating the degradation of Axin (Nature 2009, 461, 614). It has been reported that a tankyrase inhibitor accelerates the degradation of β-catenin by stabilizing Axin and inhibits Wnt/β-catenin pathway, thereby inhibiting the proliferation of a cancer cell line in which Wnt/β-catenin signaling is activated (Nature 2009, 461, 614). Therefore, such a tankyrase inhibitor is expected to be useful as a therapeutic agent for a disease in which Wnt/β-catenin signaling is activated as described above.
On the other hand, it is known that a compound represented by the following formula (A) has an adenosine uptake activity (patent document 1).

It is also known that a compound represented by the following formula (B) has a cardiotonic activity (non-patent document 1).

As a compound having a Wnt pathway inhibitory activity, a compound represented by the following formula (C) (non-patent document 2) is known.

As a compound having a tankyrase inhibitory activity, a compound represented by the following formula (D) (non-patent document 3), a compound represented by the following formula (E) (non-patent document 4), and the like are known.
